Summary: In adults with well-controlled type 2 diabetes (HbA1c ≤7.5% [≤58 mmol/mol]) on multiple daily injections of insulin (≤120 units/day), replacing prandial insulin with once-weekly subcutaneous semaglutide 1.0 mg plus basal degludec did not significantly increase the proportion maintaining target HbA1c at Week 26 (90% vs 75%, p=0.18). Secondary outcomes favoured semaglutide, with greater HbA1c reduction, marked weight loss (−8.9 kg vs +1.5 kg), and a 56% fall in insulin dose, in this small, single-centre, open-label trial.
PICO Summary
| Element | Detail |
|---|---|
| Population | 60 adults with type 2 diabetes well-controlled (HbA1c ≤7.5% [≤58 mmol/mol]) on multiple daily injections of insulin with a total daily dose ≤120 units/day; single-centre randomised open-label trial (TRANSITION-T2D), United States. |
| Intervention | Once-weekly subcutaneous semaglutide 1.0 mg plus basal insulin degludec, with prandial insulin discontinued; 2:1 allocation (n=40). |
| Comparison | Continuation of multiple daily injections (basal-bolus) prandial insulin therapy; n=20. |
| Outcome | Primary outcome (proportion maintaining HbA1c ≤7.5% at Week 26): 90% vs 75%, odds ratio 2.61 (95% CI 0.65 to 11.0), p=0.18 (not significant). Secondary outcomes (semaglutide vs MDI, mean change [95% CI]): HbA1c −0.5% (−0.7, −0.3) vs 0.0% (−0.3, 0.3), p=0.009; body weight −8.9 kg (−9.9, −7.8) vs +1.5 kg (−0.1, 3.1), p<0.001; insulin total daily dose −56.0% (−62.3, −49.7) vs +6.7% (−2.5, 16.0), p10% body weight. Hypoglycaemia frequency was similar between groups. |
Weekly semaglutide vs mealtime insulin (TRANSITION-T2D)
Open-label RCT · well-controlled type 2 diabetes · 26 weeks
Replacing mealtime insulin with weekly semaglutide did not significantly improve the proportion at HbA1c target, but markedly cut weight and insulin dose. Hypothesis-generating; frame as de-intensification, not guaranteed equivalence.
Expert Commentary
This small trial is best read as hypothesis-generating rather than confirmatory. The primary endpoint, the proportion maintaining HbA1c ≤7.5% at 26 weeks, was not met: the difference of 90% versus 75% carried a wide confidence interval (odds ratio 2.61, 0.65 to 11.0) and a non-significant p value of 0.18, so the headline question of whether semaglutide reliably preserves glycaemic control cannot be answered affirmatively here. What is more persuasive is the consistent direction of the prespecified secondary outcomes, where semaglutide produced a modest further HbA1c reduction, a substantial mean weight loss of nearly 9 kg, and a halving of insulin requirement, with prandial insulin discontinued in almost all participants and comparable hypoglycaemia. The principal limitation is the design: a single centre, only 60 participants, and an open-label structure that is liable to influence treatment-satisfaction reporting and dose titration. Can I use this with my patients? In selected well-controlled, insulin-treated patients seeking simplification and weight loss, a supervised trial of substituting prandial insulin with weekly semaglutide is reasonable, but it should be framed as de-intensification rather than guaranteed glycaemic equivalence. Larger, multi-centre, longer trials with blinded endpoint adjudication are needed before this becomes routine practice.
References
Rodriguez P, Breslaw N, Xiao H, Bena J, Jenkins K, Isaacs D, et al. De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D). Diabetes Obes Metab. 2025;27(2):642-651. doi:10.1111/dom.16057